دورية أكاديمية
Design and synthesis of a crosslinker for studying intracellular steroid trafficking pathways
| العنوان: | Design and synthesis of a crosslinker for studying intracellular steroid trafficking pathways |
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| المؤلفون: | Byrd Katherine M, Arieno Marcus D, Kennelly Megan E, Estiu Guillermina, Wiest Olaf, Helquist Paul |
| المساهمون: | Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, United States., Lab of Computational Chemistry and Drug Design, School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen 518055, China., Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, United States. Electronic address: phelquis@nd.edu. |
| المصدر: | PubMed |
| بيانات النشر: | 生物有机化学与医药化学 |
| سنة النشر: | 2015 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | Cholesterol,Crosslinker,Lysosomal,Steroid,Trafficking |
| الوصف: | A crosslinker was designed and synthesized as a molecular tool for potential use in probing the intracellular trafficking pathways of steroids. The design was guided by computational modeling based upon a model for the transfer of cholesterol between two proteins, NPC1 and NPC2. These proteins play critical roles in the transport of low-density lipoprotein-derived cholesterol from the lumen of lysosomes to other subcellular compartments. Two modified cholesterol residues were covalently joined by a tether based on molecular modeling of the transient interaction of NPC1 and NPC2 during the transfer of cholesterol from the binding site of one of these proteins to the other. With two cholesterol molecules appropriately connected, we hypothesize that the cholesterol binding sites of both proteins will be simultaneously occupied in a manner that will stabilize the protein-protein interaction to permit detailed structural analysis of the resulting complex. A photoaffinity label has also been introduced into one of the cholesterol cores to permit covalent attachment of one of the units into its respective protein-binding pocket. The basic design of these crosslinkers should render them useful for examining interactions of the NPC1/NPC2 pair as well as other sterol transport proteins.Copyright ? 2015 Elsevier Ltd. All rights reserved. ; SCI(E) ; PubMed ; 0 ; ARTICLE ; phelquis@nd.edu |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 1464-3391 |
| العلاقة: | Bioorganic & medicinal chemistry.2015.; 649527; http://hdl.handle.net/20.500.11897/188054Test |
| DOI: | 10.1016/j.bmc.2015.03.053 |
| الإتاحة: | https://doi.org/20.500.11897/188054Test https://doi.org/10.1016/j.bmc.2015.03.053Test https://hdl.handle.net/20.500.11897/188054Test |
| رقم الانضمام: | edsbas.3362822A |
| قاعدة البيانات: | BASE |
| تدمد: | 14643391 |
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| DOI: | 10.1016/j.bmc.2015.03.053 |